Inhibitory Effects of Green Tea Polyphenols on Microbial Metabolism of Aromatic Amino Acids in Humans Revealed by Metabolomic Analysis

Abstract

The bioactivities and potential health benefits of green tea polyphenols (GTP) have been extensively investigated, but the metabolic impact of chronic GTP intake on humans is not well defined. In this study, fecal and urine samples from postmenopausal female subjects taking a GTP supplement or placebo for 12 months were compared by liquid chromatography-mass spectrometry-based metabolomic analysis. The GTP-derived and GTP-responsive metabolites were identified and characterized by structural elucidation and quantitative analysis of the metabolites contributing to the separation of control and treatment samples in the multivariate models. Major GTP and their direct sulfate and glucuronide metabolites were absent in feces and urine. In contrast, GTP-derived phenyl-γ-valerlactone and phenylvaleric acid metabolites were identified as the most abundant GTP-derived metabolites in feces and urine, suggesting extensive microbial biotransformation of GTP in humans. Interestingly, GTP decreased the levels of microbial metabolites of aromatic amino acids (AAA), including indoxyl sulfate, phenylacetylglutamine, and hippuric acid, in urine. However, it did not affect the levels of AAA, as well as other microbial metabolites, including short-chain fatty acids and secondary bile acids, in feces. 16S rRNA gene sequencing indicated that the fecal microbiome was not significantly affected by chronic consumption of GTP. Overall, microbial metabolism is responsible for the formation of GTP metabolites while GTP metabolism may inhibit the formation of AAA metabolites from microbial metabolism. Because these GTP-derived and GTP-responsive metabolites have diverse bioactivities, microbial metabolism of GTP and AAA may play important roles in the beneficial health effects of green tea consumption in humans.

Tea Compounds and the Gut Microbiome: Findings from Trials and Mechanistic Studies

“…Six trials have been conducted over the last ten years looking at tea compounds and their effects on the gut microbiome [26,27,28,29,30,31]. Of these, five focused on associations between green tea and the gut microbiome [26,27,28,30,31]. Three of these were beverage trials.…”

“…Although compliance checks were undertaken, it is plausible that not all nine capsules were taken daily which could have contributed to a lack of findings. A longer 12-month study providing capsules (2 daily) containing 0.84 g epigallocatechin gallate showed that microbial metabolism was involved in the formation of green tea polyphenol metabolites and inhibited the formation of aromatic amino acid metabolism, which, together, could have a favourable role on human health [26].…”

“…Regarding quality, two of the identified trials were considered to be ‘high’ quality according to the Jadad scoring system [26,29]. The remainder were low–moderate quality.…”

Isoxanthohumol, a hop-derived flavonoid, alters the metabolomics profile of mouse feces

“…For nucleic acids, different colonic contents between GF and ex-GF mice have been reported [ 30 ]. The colonic luminal contents of nucleobase adenine, guanine, cytosine, and uracil in ex-GF mice were significantly higher than those in GF mice, perhaps reflecting the existence of intestinal bacteria.…”

“…Some food ingredients can influence the contents of fecal metabolites. For example, long-term intake of green tea extract by healthy postmenopausal females changed the fecal metabolites of aromatic amino acids (phenylacetylglutamine, hippuric acid, and indoxyl sulfate) [30]. Short-term intake of a grape seed extract increased the contents of fecal bile acids and sterols in pigs [31].…”